PRIME 细胞的 RNA 鉴定可预测类风湿关节炎的发作。
RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares.
机构信息
From the Laboratory of Molecular Neuro-oncology, Rockefeller University (D.E.O., K.S., J.F., M.O.F., S.P., N.E.B., C.H., R.B.D.), the Hospital for Special Surgery (D.E.O.), and the Simons Foundation (O.G.T.) - all in New York; Rice University, Houston (V.Y.); Princeton University, Princeton, NJ (V.Y., O.G.T.); Howard Hughes Medical Institute, Chevy Chase, MD (N.E.B., R.B.D.); and the Divisions of Rheumatology and Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, and the Broad Institute, Cambridge - both in Massachusetts (F.Z., S.R.).
出版信息
N Engl J Med. 2020 Jul 16;383(3):218-228. doi: 10.1056/NEJMoa2004114.
BACKGROUND
Rheumatoid arthritis, like many inflammatory diseases, is characterized by episodes of quiescence and exacerbation (flares). The molecular events leading to flares are unknown.
METHODS
We established a clinical and technical protocol for repeated home collection of blood in patients with rheumatoid arthritis to allow for longitudinal RNA sequencing (RNA-seq). Specimens were obtained from 364 time points during eight flares over a period of 4 years in our index patient, as well as from 235 time points during flares in three additional patients. We identified transcripts that were differentially expressed before flares and compared these with data from synovial single-cell RNA-seq. Flow cytometry and sorted-blood-cell RNA-seq in additional patients were used to validate the findings.
RESULTS
Consistent changes were observed in blood transcriptional profiles 1 to 2 weeks before a rheumatoid arthritis flare. B-cell activation was followed by expansion of circulating CD45-CD31-PDPN+ preinflammatory mesenchymal, or PRIME, cells in the blood from patients with rheumatoid arthritis; these cells shared features of inflammatory synovial fibroblasts. Levels of circulating PRIME cells decreased during flares in all 4 patients, and flow cytometry and sorted-cell RNA-seq confirmed the presence of PRIME cells in 19 additional patients with rheumatoid arthritis.
CONCLUSIONS
Longitudinal genomic analysis of rheumatoid arthritis flares revealed PRIME cells in the blood during the period before a flare and suggested a model in which these cells become activated by B cells in the weeks before a flare and subsequently migrate out of the blood into the synovium. (Funded by the National Institutes of Health and others.).
背景
类风湿关节炎与许多炎症性疾病一样，其特征是处于缓解期和加重期（发作期）之间的交替。导致发作的分子事件尚不清楚。
方法
我们制定了一项针对类风湿关节炎患者进行重复家庭采血的临床和技术方案，以进行纵向 RNA 测序（RNA-seq）。在我们的索引患者中，在 4 年的时间内，在 8 次发作中的 364 个时间点以及另外 3 名患者在发作中的 235 个时间点获得了标本。我们鉴定了在发作前差异表达的转录本，并将其与滑膜单细胞 RNA-seq 数据进行了比较。在其他患者中使用流式细胞术和分选血细胞 RNA-seq 来验证这些发现。
结果
在类风湿关节炎发作前 1 至 2 周，观察到血液转录谱的一致变化。在类风湿关节炎患者的血液中，B 细胞激活后，循环 CD45-CD31-PDPN+前炎症间充质或 PRIME 细胞扩张；这些细胞具有炎症性滑膜成纤维细胞的特征。在所有 4 名患者中，循环 PRIME 细胞水平在发作期间下降，流式细胞术和分选细胞 RNA-seq 证实了 19 名额外的类风湿关节炎患者存在 PRIME 细胞。
结论
对类风湿关节炎发作的纵向基因组分析显示，在发作前的一段时间内，血液中存在 PRIME 细胞，并提出了一种模型，即这些细胞在发作前几周被 B 细胞激活，随后从血液迁移到滑膜中。（由美国国立卫生研究院等资助）。
Zotero 插件